Niu Wei, Liu Yanlong, Dai Erling, Sun Jiarui, Dai Yuyu, Xu Xiangsheng
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.
Fuzhou Planning & Design Research Institute Group Co., Ltd, Fuzhou, 361007, P. R. China.
Org Biomol Chem. 2025 Jun 11;23(23):5533-5541. doi: 10.1039/d5ob00465a.
Isoquinoline-1,3-dione derivatives are of paramount importance in pharmaceutical research due to their versatile bioactivities, including notable anti-tumor and antibacterial properties. This study developed a novel method to synthesize amide-functionalized isoquinoline derivatives by a cascade amidation/cyclization of -(methacryloyl)benzamide with the carybamonyl radical, generated from oxamic acids with the organic photosensitizer 4CzIPN. Mechanistic investigations, supported by radical scavenger experiments and HRMS analysis, unequivocally established a radical-mediated reaction pathway, with control studies validating the proposed cyclization cascade. This protocol offers distinct advantages including mild reaction conditions, environmental benignity, and broad substrate scope for the synthesis of amide-functionalized isoquinoline-1,3-diones. Furthermore, this synthetic platform has been successfully extended to the synthesis of amide-functionalized oxindoles and succinimides bearing α-quaternary carbon centers, underscoring its broad synthetic utility.
异喹啉-1,3-二酮衍生物因其多样的生物活性，包括显著的抗肿瘤和抗菌特性，在药物研究中至关重要。本研究开发了一种新方法，通过 -(甲基丙烯酰基)苯甲酰胺与由草氨酸与有机光敏剂4CzIPN产生的卡里巴莫酰自由基进行级联酰胺化/环化反应，合成酰胺官能化的异喹啉衍生物。自由基清除剂实验和高分辨质谱分析支持的机理研究明确建立了自由基介导的反应途径，对照研究验证了所提出的环化级联反应。该方案具有明显优势，包括反应条件温和、环境友好以及合成酰胺官能化异喹啉-1,3-二酮的底物范围广泛。此外，这个合成平台已成功扩展到合成带有α-季碳中心的酰胺官能化氧化吲哚和琥珀酰亚胺，突出了其广泛的合成实用性。
